Thinking Ahead: Funding a Vaccine against EHV-1

Last night, my manfriend drove us to one of our last dinners away from the farm for the foreseeable future, and I felt my brow furrow as he handed me his cell phone and told me to read.

He had received an email with an alert for a diagnosed case of Equine Herpes Virus-1 (EHV-1) in the state of Kentucky, and was (rightfully) unnerved by what this could mean for the horses under his care. As the broodmare manager of Mt. Brilliant Farm, he was in charge of a plethora of horses – ranging from newborn foals to the pensioned mares turned out on 100 acres of lush bluegrass. These horses wellbeing and survival depended on he and his staff and EHV-1 was nothing to laugh about, especially for those of us taking care of pregnant animals.

And in the last few weeks, we had all read and heard of the cases of EHV-1 that were occurring at The Fairgrounds, a racetrack located in New Orleans, Louisiana. There had been (unsubstatiated) comments of horses leaving the facilities even after quarantine had been put in place. There had been (non validated) mentions of horses moving from barn to barn even after cases had been diagnosed.

But like most things in the horse industry, for those of us located states away, it was out of sight, out of mind.

Except for it wasn’t – at least not for me. And my boyfriend knew how closely I had been following the situation.

Over a decade ago, I worked on a ranch in Buffalo, Wyoming. Having been a guest to the ranch myself for years, I had applied at the age of 20 to be employed as a wrangler and therefore in charge of the care and training for a herd of over 150 horses. Routine lameness exams, the assessment and diagnostics of many illnesses including strangles, and even the occasional euthanasia – all of that was in the hands of the wranglers.

And with it came a plethora of stories. Of prior cases. Prior horrors. And one of those was of a horrendous outbreak of EHV-1.

And as I listened to the wranglers speak of the devastation that this outbreak left – of horses sitting on their haunches like labrador retrievers, of the chronically ill with heightened respiratory infections, and of the dozen horses that had to be euthanized – I couldn’t help but wonder.

Was it because of the level of animal husbandry that caused this outbreak? Was it the lower than usual number of vaccines that they received? The close quarters or the lack of top veterinary care?

And I walked away that summer thinking that this wouldn’t happen anywhere else. To any ONE else. But it did.

This same virus swept through the english riding facility of the University of Findlay. A top notch facility by any means, with horses who were stalled, fed, and cared for with the highest level of care. It also killed 12 horses there – leaving a devastation to the faculty and students that no one could imagine.

And at that moment I realized that no horseman was safe, and I began to dig.

Why wasn’t there a vaccine for the neurological strain? Why were we able to (for the most part) prevent the abortive aspect of this virus, but not the strain that cause this devastating incapacitation of the hind limbs?

In 2007, after hearing these horror stories from the ranch and beyond, I wrote a 13 page document in regards to a literature review on this. Under the prompting of my Cell Biology professor Dr. Ana Estevez, I chose EHV as my topic of interest for our final project.

Little was understood at that time on what mutation shifted the disease from causing a little cough and nasal discharge to that of irreversible neurodegeneration. And most papers ended with the statement that more was needed to be done, more needed to be found.

Flash forward a decade, and here I am sitting at a lab bench at one of the most famous equine research facilities in the world: The Gluck Equine Research Center. Only 12 hours after reading of the EHV-1 case that is now so much closer to home, I begin my morning by putting on a white lab coat and preparing my samples for analysis. And as I wandered down the hallways to get ice for them to thaw on, I bumped into one of the world leaders in equine virology – Dr. Udeni Balasuriya.

Dr. Balasuriya is not only brilliant, but he is also extremely amicable and his infectious laugh can be heard down the halls of Gluck on most days. And because of this, he has become one of my favorite faculty in this department.

So today, I beseeched upon him to hold the elevator and let me pester him on this topic.

And what I learned was alarming.

He told me that while the equine herpes virus-1 (EHV-1) usually only causes mild respiratory distress, it can migrate via infected white blood cells to other sites of the body including the uterus and central nervous system, leading to abortion, neonatal death, and in my experience – the severe disruption of the nervous system which leads to extreme neuropathy, now referred to as equine herpesvirus myeloencephalopathy, or EHM.

These reports of the cases of EHV currently existing in the United States would have you believe that the transfer from a simple cough to a neurological nightmare resides in a simple switch of one nucleotide, or the molecules that make up our DNA, in addition to the DNA of viruses. In science, we call these “SNPs” (single nucleotide polymorphisms), which can then completely change the amino acid and protein that they encode for.

In the EHV-1 virus, this is a switch from an A (adenine) to a G (guanine), and therefore the horses are tested for a “non-neuropathic A” or a “neuropathic G” which Dr. Balasuriya was quick to point out was far too simplistic as well as potentially dangerous.

Numerous reports have shown found horses with EHM to have a “non-neuropathic A” when one would have thought a “neuropathic G” should exist and vice versa, leading clinicians and scientists alike to promote for further research and better testing.

In a nutshell, while the horse in Northern Kentucky tested for a “neuropathic G”, and while that might be alarming, it can also be a false alarm – and the horse may only suffer from respiratory symptoms. Likewise, the horses who are testing from the “non-neuropathic A” in Louisiana may become ataxic in only a matter of days. It is, quite simply, not fool proof.

And I learned that that same outbreak at the University of Findlay had a silver lining: they were able to develop a cell culture of the neuropathic strain that had swept through their barns. Now known as T953 strain or the Findlay Strain, it was taken from a horse suffering from EHM, and is now able to be used by researchers around the world who are attempting to eradicate this disease.

I also learned that Dr. Balasuriya and his lab had been working to find a way to inhibit the pathogenicity of this virus and its potentially dehabilitating neurologic outcomes. For years now, he had worked with this neurologic strain in an attempt to figure out how to stop it. He had shown that a potent antiviral – called interferon alpha, or IFN-a – was not effective, leaving the T953 strain was resistant to its effects. But he was also able to show that the resistance of this strain to those effects was because of its ability to suppress a key aspect of cell function – the JAK-STAT pathway.

And I won’t go super sciency and try to explain this pathway, but one crucial takeway is that any dysregulation of this pathway can lead to immune disorders, or even cancer. So amazingly, the virus is able to single-handedly suppress the immune system of the very host it was invading.

And while all of this was cool, at least to the dork personified which is me, it didn’t do much to help us prevent the disease. And I asked Dr. Balasuriya that big question — WHY?

Why don’t we have a vaccine that can prevent this strain? Why don’t we have any efficacy in our coverage over the neuropathicity of this virus? And his answer was both simple and devastating….

Funding.

I have written before of this awkward state of limbo that we as researchers exist in. We have the ideas, but without the money. We have the ability, but without the support. And we have an impassioned audience – one that you as horse enthusiasts encompass, who will write a status or type out a comment in all capital letters, but who won’t then follow that up with putting money where their mouth (or fingers) are.

Researchers have access to the strain of this virus that is neuropathic, thanks in part from the blessing in disguise that was that outbreak at Findlay. They have the experimental design set up to inoculate animals with that strain in order to produce antibodies that can then be injected into horses. It would require a ton of horses to prove its efficacy, and a ton of money to perform this study, but the ability to do so exists.

So where are we, seemingly yet again? Yet again we have cases of another horrific disease that can lead to devastation – both financially and emotionally. We are watching as it spreads and wreaks its havoc, and running around like chickens with our heads cut off as we try to prevent its ability to spread even further. And yet again, we are acting retroactively instead of proactively.

In retrograde, we wait until a horse gets sick before sounding the alarms.

Proactively, we can actually develop a method to prevent that from ever happening.

So please, for the sake of our future horses and their caretakers, lets start thinking ahead instead of behind. Lets start putting our money where our outspoken mouths are and fund the researchers like Dr. Balasuriya who want to assist you in this journey, and help future generations of horsemen and women who want to do whats best for their mounts.

It takes a lot for progress to be made. It takes motivation, such as a disease outbreak. It takes intelligence, such as in the great mind of Dr. Balasuriya and his comrades that exist in these hallways of the Gluck Center. And it takes money. So please, be a part of the forward progress and donate.